{"id":39278,"date":"2026-02-02T16:18:56","date_gmt":"2026-02-02T08:18:56","guid":{"rendered":"https:\/\/www.hkioc.com.hk\/fda%e5%bf%ab%e9%80%9f%e9%80%9a%e9%81%93%e8%b3%87%e6%a0%bc%e6%8e%88%e4%ba%88%e6%96%b0%e5%9e%8b%e5%85%8d%e7%96%ab%e8%81%af%e5%90%88%e6%96%b9%e6%a1%88%ef%bc%8c%e7%94%a8%e6%96%bcmss%e8%bd%89%e7%a7%bb\/"},"modified":"2026-03-22T12:20:22","modified_gmt":"2026-03-22T04:20:22","slug":"mss-metastatic-colorectal-cancer","status":"publish","type":"post","link":"https:\/\/www.hkioc.com.hk\/en\/mss-metastatic-colorectal-cancer\/","title":{"rendered":"FDA Grants Fast Track Designation to Novel Immunotherapy Combination for MSS Metastatic Colorectal Cancer"},"content":{"rendered":"\n

1. Key Highlights<\/strong><\/p>\n\n\n\n

\u2022 A novel combination therapy consisting of an anti-CTLA-4 monoclonal antibody and a PD-1 inhibitor<\/strong> has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA)<\/strong> following promising efficacy and favourable safety results from a Phase II clinical study.<\/p>\n\n\n\n

\u2022 The anti-CTLA-4 antibody features a tumour microenvironment-selective activation (\u201cmasked\u201d) design<\/strong>, which may allow higher dosing while reducing systemic toxicity<\/strong>.<\/p>\n\n\n\n

\u2022 This approach offers a potential new immunotherapy strategy for patients with microsatellite stable (MSS) metastatic colorectal cancer<\/strong>, a group that traditionally responds poorly to conventional immune checkpoint inhibitors.<\/p>\n\n\n\n

2. Background of the Fast Track Designation<\/strong><\/h2>\n\n\n\n

The FDA recently granted Fast Track designation to muzastotug (ADG126) in combination with pembrolizumab<\/strong> for the treatment of adult patients with MSS metastatic colorectal cancer (mCRC) without active liver metastases<\/strong>.<\/p>\n\n\n\n

The decision was based on efficacy and safety data from an ongoing Phase II clinical trial<\/strong>, with updated findings presented at the 2025 ASCO Annual Meeting<\/strong>. Fast Track designation is intended to accelerate the development and regulatory review of innovative therapies that demonstrate the potential to address significant unmet medical needs<\/strong>.<\/p>\n\n\n\n

Unlike microsatellite instability-high (MSI-H) colorectal cancer<\/strong>, MSS mCRC generally shows limited response to conventional immune checkpoint inhibitors<\/strong>, and effective immunotherapy options have long been lacking.<\/p>\n\n\n\n

Muzastotug is a masked anti-CTLA-4 IgG1 monoclonal antibody<\/strong> with several key design features:<\/p>\n\n\n\n

\u2022 A cleavable masking peptide<\/strong> allows the antibody to be selectively activated within the tumour microenvironment<\/strong>.
\u2022 Binding to specific epitopes blocks CTLA-4 function<\/strong>, enhancing T-cell activation<\/strong>.
\u2022 Enhanced antibody-dependent cellular cytotoxicity (ADCC)<\/strong> or phagocytosis<\/strong> may help reduce the level of immunosuppressive regulatory T cells within the tumour environment.<\/p>\n\n\n\n

This design may allow the therapy to be administered at higher doses when combined with PD\u20111 inhibitors, theoretically improving efficacy while reducing systemic immune\u2011related toxicity. As a result, it provides a new immunomodulatory pathway for MSS colorectal cancer patients<\/strong>.<\/p>\n\n\n\n

3. Current Clinical Development<\/strong><\/h2>\n\n\n\n

The ongoing randomised Phase II study<\/strong> is designed as follows:<\/p>\n\n\n\n

Patients are randomly assigned to receive muzastotug at 10 mg\/kg or 20 mg\/kg<\/strong>, in combination with pembrolizumab<\/strong>.<\/p>\n\n\n\n

The treatment follows an induction-maintenance dosing strategy<\/strong>. No monotherapy control arm is included, and each dose group plans to enrol approximately 30 patients<\/strong>.<\/p>\n\n\n\n

Eligibility criteria include:<\/p>\n\n\n\n

\u2022 Adults aged 18 years or older<\/strong> with MSS metastatic colorectal cancer
\u2022 ECOG performance status of 0\u20131<\/strong>
<\/strong> \u2022 At least one measurable lesion<\/strong> according to RECIST 1.1 criteria<\/strong>
<\/strong> \u2022 Adequate organ function
\u2022 Availability of tumour tissue samples collected within the two years prior to enrolment<\/strong><\/p>\n\n\n\n

The primary study endpoints include maximum tolerated dose (MTD)<\/strong>, recommended Phase II dose<\/strong>, safety<\/strong>, tolerability<\/strong>, and preliminary anti-tumour activity<\/strong>.<\/p>\n\n\n\n

4. Efficacy and Safety Data<\/strong><\/h2>\n\n\n\n

Data presented at the ASCO Annual Meeting<\/strong> showed the following results:<\/p>\n\n\n\n

In the 10 mg\/kg cohort (n=29)<\/strong>:<\/p>\n\n\n\n

\u2022 Objective response rate (ORR): 17%<\/strong>
<\/strong> \u2022 Disease control rate (DCR): 76%<\/strong>
<\/strong> \u2022 6-month clinical benefit rate: 38%<\/strong>
<\/strong> \u2022 Median progression-free survival (PFS): 4.8 months<\/strong>
<\/strong> \u2022 Median duration of response (DOR): 6.2 months<\/strong><\/p>\n\n\n\n

In the 20 mg\/kg cohort (n=21)<\/strong>:<\/p>\n\n\n\n

\u2022 ORR: 29%<\/strong>
<\/strong> \u2022 DCR: 81%<\/strong>
<\/strong> \u2022 Median PFS: not yet reached<\/strong>
<\/strong> \u2022 6-month PFS rate: approximately 50%<\/strong><\/p>\n\n\n\n

At a median follow-up of 17.8 months<\/strong>, the overall median overall survival (OS)<\/strong> reached 19.4 months<\/strong>.<\/p>\n\n\n\n

5. Safety Profile<\/strong><\/h2>\n\n\n\n

Treatment-related adverse events were relatively common in both dose groups but were generally manageable<\/strong>.<\/p>\n\n\n\n

Common adverse reactions included:<\/p>\n\n\n\n

\u2022 Pruritus (itching)
\u2022 Diarrhoea
\u2022 Hypothyroidism
\u2022 Fatigue
\u2022 Adrenal insufficiency<\/p>\n\n\n\n

Importantly:<\/p>\n\n\n\n

\u2022 No dose-limiting toxicities were observed<\/strong>
<\/strong> \u2022 No grade 4 or grade 5 treatment-related adverse events occurred<\/strong>
<\/strong> \u2022 The treatment discontinuation rate due to adverse events was approximately 4%<\/strong><\/p>\n\n\n\n

6. Next Steps<\/strong><\/h2>\n\n\n\n

Based on the current study findings and regulatory feedback, a registrational Phase III clinical trial<\/strong> is expected to begin in 2027<\/strong>.<\/p>\n\n\n\n

The primary endpoint will be overall survival (OS)<\/strong>, with secondary endpoints including:<\/p>\n\n\n\n

\u2022 Progression-free survival (PFS)
\u2022 Duration of response (DOR)
\u2022 Objective response rate (ORR)<\/p>\n\n\n\n

The control arm will use the current standard-of-care treatment<\/strong>.<\/p>\n\n\n\n

In the field of MSS metastatic colorectal cance<\/a>r<\/strong>, where immunotherapy has historically been difficult to advance, combination immunotherapy strategies based on masked anti-CTLA-4 antibodies are gradually demonstrating clinical potential<\/strong>.<\/p>\n","protected":false},"excerpt":{"rendered":"

This approach offers a potential new immunotherapy strategy for patients with microsatellite stable (MSS) metastatic colorectal cancer, a group that traditionally responds poorly to conventional immune checkpoint inhibitors.<\/p>\n","protected":false},"author":14,"featured_media":38184,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1739,1767],"tags":[],"yst_prominent_words":[],"class_list":["post-39278","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-colorectal-cancer","category-treatment"],"_links":{"self":[{"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/posts\/39278","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/users\/14"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/comments?post=39278"}],"version-history":[{"count":2,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/posts\/39278\/revisions"}],"predecessor-version":[{"id":39281,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/posts\/39278\/revisions\/39281"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/media\/38184"}],"wp:attachment":[{"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/media?parent=39278"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/categories?post=39278"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/tags?post=39278"},{"taxonomy":"yst_prominent_words","embeddable":true,"href":"https:\/\/www.hkioc.com.hk\/en\/wp-json\/wp\/v2\/yst_prominent_words?post=39278"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}